Vallera Daniel A, Elson Michael, Brechbiel Martin W, Dusenbery Kathryn E, Burns Linda J, Jaszcz Waclaw B, Ramsay Norma K, Panoskaltsis-Mortar Angela, Kuroki David W, Wagner John E, Vitetta Ellen S, Kersey John H
Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Cancer Center, Minneapolis, MN, USA.
Cancer Biother Radiopharm. 2004 Feb;19(1):11-23. doi: 10.1089/108497804773391630.
Studies were performed to determine the suitability of using two different anti-CD19 monoclonal antibodies to deliver the high energy beta-particle emitting isotope 90Y to B-cell lymphoma grown as flank tumors in athymic nude mice. The antibodies BU12 and HD37, both of the IgG1 subclass, recognize CD19, an internalizing B-lineage-specific membrane glycoprotein and member of the Ig supergene family. The antibodies were readily labeled with 90Y using the highly stable chelate, 1B4M-MX-DTPA. The radioimmunoconjugates selectively bound to the CD19 expressing B cell line Daudi, but not to CD19 negative control cells. Significantly more 90Y anti-CD19 bound to Daudi tumors growing in nude mice than did a control non-binding antibody (p = 0.001). The biodistribution data correlated with an anti-tumor effect. Anti-tumor activity was dose dependent and the best results were observed in mice receiving a single dose of approximately 300 uCi. The anti-CD19 antibody had significantly better anti-tumor activity as compared to a control 90Y-labeled antibody and most mice survived over 119 days with no evidence of tumor (p < 0.003). Histology studies showed no significant injury to the kidney, liver, or small intestine. Because radiolabeled anti-CD19 antibody can be used to deliver radiation selectively to lymphohematopoietic tissue, these data support the use of 90Y anti-CD19 antibodies in treating B-cell malignancies.
开展了多项研究，以确定使用两种不同的抗CD19单克隆抗体将发射高能β粒子的同位素90Y递送至在无胸腺裸鼠胁腹生长的B细胞淋巴瘤的适用性。抗体BU12和HD37均为IgG1亚类，它们识别CD19，CD19是一种内化的B谱系特异性膜糖蛋白，属于Ig超基因家族成员。使用高度稳定的螯合剂1B4M-MX-DTPA可轻松用90Y标记这些抗体。放射性免疫缀合物选择性地结合表达CD19的B细胞系Daudi，但不结合CD19阴性对照细胞。与对照非结合抗体相比，显著更多的90Y抗CD19抗体结合到裸鼠体内生长的Daudi肿瘤上（p = 0.001）。生物分布数据与抗肿瘤作用相关。抗肿瘤活性呈剂量依赖性，在接受单剂量约300 μCi的小鼠中观察到最佳结果。与对照90Y标记抗体相比，抗CD19抗体具有显著更好的抗肿瘤活性，大多数小鼠存活超过119天且无肿瘤迹象（p < 0.003）。组织学研究表明，对肾脏、肝脏或小肠无明显损伤。由于放射性标记的抗CD19抗体可用于将辐射选择性地递送至淋巴造血组织，这些数据支持使用90Y抗CD19抗体治疗B细胞恶性肿瘤。
